Quantitative Imaging of Mouse Brain Development

小鼠大脑发育的定量成像

• 批准号: 10362680
• 负责人: JIANGYANG ZHANG
• 金额: $ 59.33万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362680
• 关键词: 3-Dimensional; 4D MRI; Adolescence; Anatomy; Area; Atlases; Axon; BRAIN initiative; Biological Models; Brain; Brain Injuries; Brain region; Cellularity; Complex; Computational Technique; Consumption; Data; Defect; Development; Developmental Biology; Developmental Process; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Embryo; Embryonic Development; Event; Genes; Genetic; Genetic study; Goals; Histologic; Histology; Human; Image; Image Analysis; Imaging Device; Imaging Techniques; Knockout Mice; Knowledge; Location; Magnetic Resonance Imaging; Manganese; Maps; Measurement; Microcephaly; Midbrain structure; Modeling; Molecular; Monitor; Morphology; Mouse Strains; Mus; Mutant Strains Mice; Neurodevelopmental Disorder; Neuronal Differentiation; Neurons; Pattern; Phenotype; Physics; Process; Protocols documentation; Research; Resolution; Signal Transduction; TP53 gene; Techniques; Technology; Time; Tissues; Toxic effect; United States National Institutes of Health; Wild Type Mouse; automated image analysis; base; brain abnormalities; brain magnetic resonance imaging; brain morphology; contrast imaging; cortex mapping; fetal; imaging biomarker; in utero; in vivo; innovation; interest; longitudinal analysis; migration; mind control; mouse development; mouse model; mutant mouse model; neonatal brain development; neonatal mice; neuronal patterning; new technology; novel; performance tests; postnatal; prenatal; programs; quantitative imaging; spatiotemporal; stem; tool

Abstract: Brain development is a highly dynamic yet precisely orchestrated process. Using genetically modified mouse models, we are in the process of unveiling the complex mechanisms that control critical cellular events in the developing brain. High-throughput imaging tools will greatly benefit studies in this area by charactering brain phenotypes at the macroscopic/mesoscopic levels and directing subsequent examinations at the cellular and molecular levels. In this project, multiple novel magnetic resonance imaging (MRI) techniques will be developed to non-invasively exam a wide range of phenotypes in the developing mouse brain from mid- embryonic stage to adolescence. The target phenotypes include macroscopic brain morphology and structural connectivity, microstructural organization, neuronal migration and differentiation, and postnatal brain activity. The proposed techniques include fast imaging sequences, novel image contrasts, optimized imaging coils/holder, and image analysis tools, many of which stem from on our existing expertise. In Aim 1, we will develop imaging tools to achieve high-throughput in vivo multi-contrast MRI of the developing mouse brain. We will collect multi-contrast MRI data to construct an in vivo MRI atlas of the developing mouse brain to assist mouse brain phenotype analysis and use the sas4-/- mouse, a model of microcephaly, to test the performance of the technique. In Aim 2, we will use novel diffusion MRI techniques to characterize macroscopic morphology, connectivity, and microstructural organization in the developing brain. In particular, high angular resolution diffusion imaging (HARDI) will be used to resolve complex tissue microstructural organization and reconstruct connectivity between major brain regions, and the new oscillating gradient diffusion MRI technique will be used to exam changes in cellularity in the developing cortex associated with neuronal migration. Detailed examination of the relationships between diffusion MRI-based markers and specific histological markers will determine their sensitivity to the underlying developmental processes. In Aim 3, we will use novel Manganese (Mn2+)-enhanced MRI as another tissue contrast, which reflects postnatal brain activity and potentially neuronal differentiation in the embryonic brain, to examine the developing mouse brain. We will examine the contrast patterns of Mn2+-enhanced MRI in the embryonic and neonatal mouse brain with the patterns of neuronal differentiation observed in histological data to determine the sensitivity of Mn2+-enhanced MRI to neuronal differentiation. In addition, we will investigate potential toxic effects of Mn2+ on brain development, and establish protocols that minimize these effects. In Aims 2 and 3, the techniques will also be used to characterize three mutant mouse models with abnormal brain phenotypes resulting from defects in neuronal migration and differentiation. The imaging techniques and knowledge gained in this project will greatly enhance our ability to quantitatively characterize the phenotypes of mutant mouse models in order to achieve a deep understanding of brain development and disorders.

摘要： 大脑发育是一个高度动态但精确协调的过程。使用转基因老鼠 模型，我们正在揭示控制关键细胞事件的复杂机制， 大脑发育高通量成像工具将极大地有利于这一领域的研究， 表型在宏观/介观水平，并指导随后的检查，在细胞和 分子水平。在这个项目中，多种新的磁共振成像（MRI）技术将被 开发非侵入性检查广泛的表型在发育中的小鼠大脑从中期， 胚胎期到青春期。目标表型包括宏观脑形态和结构 连接性、微结构组织、神经元迁移和分化以及出生后大脑活动。 所提出的技术包括快速成像序列、新颖的图像对比度、优化成像 线圈/保持器和图像分析工具，其中许多都源于我们现有的专业知识。 在目标1中，我们将开发成像工具，以实现高通量的在体多对比MRI， 发育中的老鼠大脑我们将收集多对比MRI数据，以构建一个体内MRI图谱， 开发小鼠脑以辅助小鼠脑表型分析， 使用sas 4-/-鼠标， 小头畸形，以测试该技术的性能。 在目标2中，我们将使用新的弥散MRI技术， 表征发育中大脑的宏观形态、连通性和微观结构组织。 特别是，将使用高角分辨率扩散成像（HARDI）来分辨复杂组织 微观结构组织和重建主要大脑区域之间的连接，以及新的振荡 梯度扩散MRI技术将用于检查发育中皮质中细胞结构的变化 与神经元迁移有关。详细检查基于扩散MRI的 标记物和特异性组织学标记物将决定它们对潜在发育的敏感性。 流程.在目标3中，我们将使用新型锰（Mn 2+）增强MRI作为另一种组织对比剂， 反映了出生后的大脑活动和胚胎大脑中潜在的神经元分化， 发育中的老鼠大脑我们将检查胚胎和胚胎中Mn 2+增强MRI的对比模式， 用新生小鼠脑神经元分化的模式观察组织学资料，以确定 Mn 2+增强MRI对神经元分化的敏感性。 此外，我们将调查潜在的有毒物质， Mn 2+对大脑发育的影响，并建立最大限度地减少这些影响的协议。在目标2和3中， 技术也将被用来描述三种具有异常脑表型的突变小鼠模型 由于神经元迁移和分化缺陷而导致。所获得的成像技术和知识 将大大提高我们定量表征突变小鼠表型的能力 模型，以实现对大脑发育和疾病的深入了解。

项目成果

Macroscopic Structural and Connectome Mapping of the Mouse Brain Using Diffusion Magnetic Resonance Imaging.

• DOI: 10.21769/bioprotoc.4221
• 发表时间: 2021-11-20
• 期刊: Bio-protocol
• 影响因子: 0.8
• 作者: Arefin TM;Lee CH;White JD;Zhang J;Kaffman A
• 通讯作者: Kaffman A

Activation of RhoC by regulatory ubiquitination is mediated by LNX1 and suppressed by LIS1.

• DOI: 10.1038/s41598-022-19740-1
• 发表时间: 2022-10-03
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Kholmanskikh, Stanislav;Singh, Shawn;Ross, M. Elizabeth
• 通讯作者: Ross, M. Elizabeth

Inhomogeneous magnetization transfer MRI of white matter structures in the hypomyelinated shiverer mouse brain.

• DOI: 10.1002/mrm.29207
• 发表时间: 2022-07
• 期刊: MAGNETIC RESONANCE IN MEDICINE
• 影响因子: 3.3
• 作者: Lee, Choong Heon;Walczak, Piotr;Zhang, Jiangyang
• 通讯作者: Zhang, Jiangyang

Oscillating gradient diffusion kurtosis imaging of normal and injured mouse brains.

正常和受伤小鼠大脑的振荡梯度扩散峰度成像。

• DOI: 10.1002/nbm.3917
• 发表时间: 2018
• 期刊: NMR in biomedicine
• 影响因子: 2.9
• 作者: Wu,Dan;Li,Qiang;Northington,FrancesJ;Zhang,Jiangyang
• 通讯作者: Zhang,Jiangyang

Virtual mouse brain histology from multi-contrast MRI via deep learning.

• DOI: 10.7554/elife.72331
• 发表时间: 2022-01-28
• 期刊: eLife
• 影响因子: 7.7
• 作者: Liang Z;Lee CH;Arefin TM;Dong Z;Walczak P;Shi SH;Knoll F;Ge Y;Ying L;Zhang J
• 通讯作者: Zhang J